From the Guidelines
Insulin deficit in patients with type 2 diabetes is primarily caused by a combination of insulin resistance and progressive beta cell dysfunction, as evidenced by the most recent study 1. The pathophysiology of type 2 diabetes involves a complex interplay of factors, including genetic predisposition, environmental factors, and lifestyle choices.
- Insulin resistance, which is often associated with obesity, physical inactivity, and poor diet, plays a significant role in the development of type 2 diabetes.
- As the disease progresses, the pancreatic beta cells become increasingly dysfunctional, leading to a decline in insulin secretion and an inability to maintain normal blood glucose levels. Key factors contributing to beta cell failure include:
- Chronic exposure to elevated glucose levels (glucotoxicity)
- High free fatty acid levels (lipotoxicity)
- Oxidative stress
- Inflammatory processes
- Amyloid deposits in the pancreatic islets The progression of type 2 diabetes typically involves a gradual decline in beta cell function, with patients losing approximately 50-60% of their beta cell function by the time of diagnosis, as supported by earlier studies 1. However, the most recent and highest quality study 1 provides the most up-to-date understanding of the causes of insulin deficit in type 2 diabetes, emphasizing the importance of insulin resistance and beta cell dysfunction. Lifestyle factors, such as obesity, physical inactivity, and poor diet, accelerate this process by worsening insulin resistance and placing greater demand on the already compromised beta cells. As the disease advances, the insulin deficit becomes more pronounced, often necessitating insulin therapy in later stages.
From the Research
Causes of Insulin Deficit in Type 2 Diabetes
The causes of insulin deficit in patients with type 2 diabetes are multifaceted and involve both genetic and acquired components. Some key factors include:
- Impaired insulin secretion due to functional and survival defects of the beta-cell 2, 3, 4, 5, 6
- Insulin resistance, which can be acquired due to unhealthy lifestyles such as obesity and physical inactivity 3, 4, 5
- Reduced beta-cell mass and functional abnormalities that make the beta-cell unable to compensate for increased insulin requirements caused by insulin resistance 3, 5
- Glucotoxicity and lipotoxicity, which can contribute to the continuous decline of beta-cell function 2, 5
- Genetic predisposition to impaired insulin secretion, which can be detected before insulin resistance 4
Mechanisms of Insulin Deficit
The mechanisms of insulin deficit in type 2 diabetes involve:
- Abnormal pulsatility of basal insulin secretion and loss of first-phase insulin release in response to a glucose challenge 2, 5
- Progressive reduction of function and mass of beta-cells, leading to a decrease in insulin secretion 5
- Disturbance in the endocrine activity of the pancreas, including an increase in fasting plasma glucagon and impaired suppression after the ingestion of an oral glucose load 5
- Reduction of the insulin:glucagon molar ratio, which affects hepatic glucose production and contributes to fasting hyperglycemia and excessive post-prandial glucose rise 5